Computational Enterprise Modeling and Simulation: Enabling Enterprise Performance Improvement, Modernization and Transformation

Lean Advancement Initiative Annual Conference presentatio

Increasing Value of a Family of Products through Flexibility: Hedging Against Uncertainty

LAI Annual Meeting presentation from the session, Pushing the Enterprise Modeling Envelop

Exploitation of Other Social Amoebae by Dictyostelium caveatum

Dictyostelium amoebae faced with starvation trigger a developmental program during which many cells aggregate and form fruiting bodies that consist of a ball of spores held aloft by a thin stalk. This developmental strategy is open to several forms of exploitation, including the remarkable case of Dictyostelium caveatum, which, even when it constitutes 1/10(3) of the cells in an aggregate, can inhibit the development of the host and eventually devour it. We show that it accomplishes this feat by inhibiting a region of cells, called the tip, which organizes the development of the aggregate into a fruiting body. We use live-cell microscopy to define the D. caveatum developmental cycle and to show that D. caveatum amoebae have the capacity to ingest amoebae of other Dictyostelid species, but do not attack each other. The block in development induced by D. caveatum does not affect the expression of specific markers of prespore cell or prestalk cell differentiation, but does stop the coordinated cell movement leading to tip formation. The inhibition mechanism involves the constitutive secretion of a small molecule by D. caveatum and is reversible. Four Dictyostelid species were inhibited in their development, while D. caveatum is not inhibited by its own compound(s). D. caveatum has evolved a predation strategy to exploit other members of its genus, including mechanisms of developmental inhibition and specific phagocytosis

Effect of formant frequency spacing on perceived gender in pre-pubertal children's voices

<div><p>Background</p><p>It is usually possible to identify the sex of a pre-pubertal child from their voice, despite the absence of sex differences in fundamental frequency at these ages. While it has been suggested that the overall spacing between formants (formant frequency spacing - ΔF) is a key component of the expression and perception of sex in children's voices, the effect of its continuous variation on sex and gender attribution has not yet been investigated.</p><p>Methodology/Principal findings</p><p>In the present study we manipulated voice ΔF of eight year olds (two boys and two girls) along continua covering the observed variation of this parameter in pre-pubertal voices, and assessed the effect of this variation on adult ratings of speakers' sex and gender in two separate experiments. In the first experiment (sex identification) adults were asked to categorise the voice as either male or female. The resulting identification function exhibited a gradual slope from male to female voice categories. In the second experiment (gender rating), adults rated the voices on a continuum from “masculine boy” to “feminine girl”, gradually decreasing their masculinity ratings as ΔF increased.</p><p>Conclusions/Significance</p><p>These results indicate that the role of ΔF in voice gender perception, which has been reported in adult voices, extends to pre-pubertal children's voices: variation in ΔF not only affects the perceived sex, but also the perceived masculinity or femininity of the speaker. We discuss the implications of these observations for the expression and perception of gender in children's voices given the absence of anatomical dimorphism in overall vocal tract length before puberty.</p></div

Longitudinal impact of a youth tobacco education program

BACKGROUND: Information on the effectiveness of elementary school level, tobacco-use prevention programs is generally limited. This study assessed the impact of a structured, one-time intervention that was designed to modify attitudes and knowledge about tobacco. Participants were fifth-grade students from schools in western New York State. METHODS: Twenty-eight schools, which were in relatively close geographic proximity, were randomized into three groups; Group 1 was used to assess whether attitudes/knowledge were changed in the hypothesized direction by the intervention, and if those changes were retained four months later. Groups 2 and 3, were used as comparison groups to assess possible test-retest bias and historical effects. Groups 1 and 3 were pooled to assess whether attitudes/knowledge were changed by the intervention as measured by an immediate post-test. The non-parametric analytical techniques of Wilcoxon-Matched Pairs/Sign Ranks and the Mann-Whitney-Wilcoxon Rank Sums Tests were used to compare proportions of correct responses at each of the schools. RESULTS: Pooled analyses showed that short-term retention on most items was achieved. It was also found that retention on two knowledge items 'recognition that smokers have yellow teeth and fingers' and 'smoking one pack of cigarettes a day costs several hundred dollars per year' was maintained for four months. CONCLUSIONS: The findings suggest that inexpensive, one-time interventions for tobacco-use prevention can be of value. Changes in attitudes and knowledge conducive to the goal of tobacco-use prevention can be achieved for short-term retention and some relevant knowledge items can be retained for several months

Natural course of behavioral addictions: A 5-year longitudinal study

BACKGROUND: Resolving the theoretical controversy on the labeling of an increasing number of excessive behaviors as behavioral addictions may also be facilitated by more empirical data on these behavioral problems. For instance, an essential issue to the classification of psychiatric disorders is information on their natural course. However, longitudinal research on the chronic vs. episodic nature of behavioral addictions is scarce. The aim of the present study, therefore, was to provide data on prevalence, substance use comorbidity, and five-year trajectories of six excessive behaviors—namely exercising, sexual behavior, shopping, online chatting, video gaming, and eating. METHODS: Analyses were based on the data of the Quinte Longitudinal Study, where a cohort of 4,121 adults from Ontario, Canada was followed for 5 years (2006 to 2011). The response rate was 21.3%, while retention rate was 93.9%. To assess the occurrence of each problem behavior, a single self-diagnostic question asked people whether their over-involvement in the behavior had caused significant problems for them in the past 12 months. To assess the severity of each problem behavior reported, the Behavioral Addiction Measure was administered. A mixed design ANOVA was used to investigate symptom trajectories over time for each problem behavior and whether these symptom trajectories varied as a function of sex. RESULTS: The large majority of people reported having problematic over-involvement for just one of these behaviors and just in a single time period. A main effect of time was found for each problem behavior, indicating a moderately strong decrease in symptom severity across time. The time x sex interaction was insignificant in each model indicating that the decreasing trend is similar for males and females. The data also showed that help seeking was very low in the case of excessive sexual behavior, shopping, online chatting, and video gaming but substantially more prevalent in the case of excessive eating and exercising. CONCLUSIONS: The present results indicate that self-identified excessive exercising, sexual behavior, shopping, online chatting, video gaming, and/or eating tend to be fairly transient for most people. This aspect of the results is inconsistent with conceptualizations of addictions as progressive in nature, unless treated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-015-0383-3) contains supplementary material, which is available to authorized users

eIF2α Kinases Regulate Development through the BzpR Transcription Factor in Dictyostelium discoideum

A major mechanism of translational regulation in response to a variety of stresses is mediated by phosphorylation of eIF2α to reduce delivery of initiator tRNAs to scanning ribosomes. For some mRNAs, often encoding a bZIP transcription factor, eIF2α phosphorylation leads to enhanced translation due to delayed reinitiation at upstream open reading frames. Dictyostelium cells possess at least three eIF2α kinases that regulate various portions of the starvation-induced developmental program. Cells possessing an eIF2α that cannot be phosphorylated (BS167) show abnormalities in growth and development. We sought to identify a bZIP protein in Dictyostelium whose production is controlled by the eIF2α regulatory system.Cells disrupted in the bzpR gene had similar developmental defects as BS167 cells, including small entities, stalk defects, and reduced spore viability. β-galactosidase production was used to examine translation from mRNA containing the bzpR 5' UTR. While protein production was readily apparent and regulated temporally and spatially in wild type cells, essentially no β-galactosidase was produced in developing BS167 cells even though the lacZ mRNA levels were the same as those in wild type cells. Also, no protein production was observed in strains lacking IfkA or IfkB eIF2α kinases. GFP fusions, with appropriate internal controls, were used to directly demonstrate that the bzpR 5' UTR, possessing 7 uORFs, suppressed translation by 12 fold. Suppression occurred even when all but one uORF was deleted, and translational suppression was removed when the ATG of the single uORF was mutated.The findings indicate that BzpR regulates aspects of the development program in Dictyostelium, serving as a downstream effector of eIF2α phosphorylation. Its production is temporally and spatially regulated by eIF2α phosphorylation by IfkA and IfkB and through the use of uORFs within the bzpR 5' UTR

Numerical Analysis of Ca2+ Signaling in Rat Ventricular Myocytes with Realistic Transverse-Axial Tubular Geometry and Inhibited Sarcoplasmic Reticulum

The t-tubules of mammalian ventricular myocytes are invaginations of the cell membrane that occur at each Z-line. These invaginations branch within the cell to form a complex network that allows rapid propagation of the electrical signal, and hence synchronous rise of intracellular calcium (Ca2+). To investigate how the t-tubule microanatomy and the distribution of membrane Ca2+ flux affect cardiac excitation-contraction coupling we developed a 3-D continuum model of Ca2+ signaling, buffering and diffusion in rat ventricular myocytes. The transverse-axial t-tubule geometry was derived from light microscopy structural data. To solve the nonlinear reaction-diffusion system we extended SMOL software tool (http://mccammon.ucsd.edu/smol/). The analysis suggests that the quantitative understanding of the Ca2+ signaling requires more accurate knowledge of the t-tubule ultra-structure and Ca2+ flux distribution along the sarcolemma. The results reveal the important role for mobile and stationary Ca2+ buffers, including the Ca2+ indicator dye. In agreement with experiment, in the presence of fluorescence dye and inhibited sarcoplasmic reticulum, the lack of detectible differences in the depolarization-evoked Ca2+ transients was found when the Ca2+ flux was heterogeneously distributed along the sarcolemma. In the absence of fluorescence dye, strongly non-uniform Ca2+ signals are predicted. Even at modest elevation of Ca2+, reached during Ca2+ influx, large and steep Ca2+ gradients are found in the narrow sub-sarcolemmal space. The model predicts that the branched t-tubule structure and changes in the normal Ca2+ flux density along the cell membrane support initiation and propagation of Ca2+ waves in rat myocytes

A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa

BACKGROUND: Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes. RESULTS: We present a detailed sequence analysis of the 10 formins (ForA to J) identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells. CONCLUSION: Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism